Role of TIM-4 in exosome-dependent entry of HIV-1 into human immune cells.
Role of TIM-4 in exosome-dependent entry of HIV-1 into human immune cells.
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DOI：
10.2147/ijn.s132762
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发表时间：
2017
影响因子：
8
通讯作者：
Matthews QL
中科院分区：
文献类型：
--
作者：
Sims B;Farrow AL;Williams SD;Bansal A;Krendelchtchikov A;Gu L;Matthews QL
外泌体是由供体细胞分泌并被受体细胞内化的30-200 nm纳米结构，在某些病毒进入细胞中起重要作用。这些微泡活跃地分泌到各种体液中，包括血液、尿液、唾液、脑脊液和母乳。我们成功地从人母乳和血浆中分离出外泌体。通过纳米颗粒跟踪测量纯化外泌体的大小和浓度，而Western blotting证实外泌体相关蛋白CD9和CD63、网格蛋白、T细胞免疫球蛋白和粘蛋白（TIMs）的存在。通过病毒感染试验，我们确定HIV-1利用外泌体依赖机制进入人类免疫细胞。该病毒含有大量的磷脂酰丝氨酸（PtdSer），并可结合PtdSer受体，如TIMs。我们的研究结果支持了这一机制，即来自多种来源的外泌体增加了HIV-1进入T细胞和巨噬细胞，并且抗tim -4抗体有效地阻止了病毒的进入。
Exosomes, 30–200 nm nanostructures secreted from donor cells and internalized by recipient cells, can play an important role in the cellular entry of some viruses. These microvesicles are actively secreted into various body fluids, including blood, urine, saliva, cerebrospinal fluid, and breast milk. We successfully isolated exosomes from human breast milk and plasma. The size and concentration of purified exosomes were measured by nanoparticle tracking, while Western blotting confirmed the presence of the exosomal-associated proteins CD9 and CD63, clathrin, and T cell immunoglobulin and mucin proteins (TIMs). Through viral infection assays, we determined that HIV-1 utilizes an exosome-dependent mechanism for entry into human immune cells. The virus contains high amounts of phosphatidylserine (PtdSer) and may bind PtdSer receptors, such as TIMs. This mechanism is supported by our findings that exosomes from multiple sources increased HIV-1 entry into T cells and macrophages, and viral entry was potently blocked with anti-TIM-4 antibodies.